Chemotherapy is the treatment of cancer with one or more cytotoxic antineoplastic drugs as part of a standardized regimen. Most chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles, which result in the most common side-effects of chemotherapy: decreased production of blood cells, inflammation of the digestive tract lining, and hair loss.
Most of the conventional chemotherapeutic agents have poor pharmacokinetics profiles and are distributed non-specifically in the body leading to systemic toxicity associated with the above mentioned side effects. Therefore, the development of drug delivery systems able to target the tumor site is becoming a real challenge that is currently addressed.
Targeted therapy is one approach for overcoming the non-specificity of the chemotherapeutic agents. In this approach the chemotherapeutic agents block the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Using nano-carriers is an additional developing tactic for specifically delivering the chemotherapeutic agents to their target. The nano-carriers are able to target the drug to the tumor site and specifically deliver it there, thereby reducing the damage to normal tissues.
In another approach, an inactive form (pro-drug) of a therapeutic agent is systematically introduced and then specifically activated by external high-energy ionizing radiation aimed explicitly to the target site. For example, U.S. Pat. No. 6,159,443 recites a method in which a target tissue is exposed to ionizing radiation before, after, or in parallel to the administration of a delivery vehicle which is platelets or proteins which bind activated platelets, comprising an active agent. The ionizing radiation induces an inflammatory response which causes the delivery vehicle to aggregate in the target tissue and thereby deliver the agent to the target tissue. Another example can be found in U.S. Pat. No. 5,962,424 which discloses a method for specifically targeting L-selectin or E-selectin binding agents by ionizing radiation. It is disclosed in U.S. Pat. No. 5,962,424 that the ionizing radiation induces L-selectin or E-selectin expression on the surface of vasculature endothelial cells.
In the above examples, the ionizing radiation is administered to the treated subject to produce an effect on a tissue that will enable the drug specificity. Furthermore, the ionizing radiation also affects regions preceding and following the target tissue, thus damaging healthy tissue which will cause adverse effects. In addition, if not delivered by a beam having a sufficient dosage specifically at the target site, the ionizing radiation will also activate tissues or molecules surrounding the target area.
There thus remains a long felt need for a method and device that will deliver ionizing radiation for activating a pro-drug in an effective manner that will not cause its activation in tissues preceding or following the target tissue nor in tissues surrounding the target tissue.